Multi-spectral fluorescence imaging with optical efficiency

Abstract

In certain embodiments, a system, computer-implemented method, and computer-readable medium for light-efficient fluorescence imaging are disclosed. The retina is flickered with broadband light, and the return light is imaged after passing through one or more filters, such as a notch filter, a low pass filter, and a high pass filter. Images may be captured with a single camera or at least two cameras, one capturing transmitted light from the filter and the other capturing return light. The images may be combined by subtraction and / or addition to obtain a combined image representing light within the passband without using a passband filter during imaging.

Description

Background Art

[0001] The diagnosis and treatment of many ocular disorders requires imaging of the patient's eye. The retina has many complex features that are imaged for diagnosis of ocular disorders as well as other disorders that cause physiological changes in the retina. Some features corresponding to healthy ocular anatomy or pathologies will exhibit fluorescence when illuminated. The spectral "fingerprint" of this fluorescence can be used as a biomarker corresponding to a specific pathology. For example, fundus autofluorescence imaging (FAF) is often used to diagnose retinal degenerative diseases.

[0002] Existing methods for measuring fluorescence use complex and expensive spectrometers to detect the spectrum of reflected light, but their ability to detect spatial information of the retina is limited. As a result, diagnosis of some diseases requires expensive testing at a small number of institutions with the required expertise and equipment.

[0003] It would be an advance in the art to improve the accessibility of fluorescence imaging and combine the fluorescence information with spatial information related to the patient's retina. Summary of the invention

[0004] In certain embodiments, a system is provided, the system comprising one or more processing devices and one or more memory devices coupled to the one or more processing devices. The one or more memory devices store executable code that, when executed by the one or more processing devices, causes the one or more processing devices to receive a first image of a first light reflected from a retina of a patient and filtered according to a first filtering. A second image is received, the second image being a second image of a second light reflected from a retina of the patient and filtered according to a second filtering. The first image and the second image are combined to obtain a combined image representing a portion of at least one of the first light and the second light within a passband, neither the first filtering nor the second filtering comprising a passband filtering. The combined image can be output to a display device. BRIEF DESCRIPTION OF THE DRAWINGS

[0005] In order to be able to understand the above-mentioned features of the present disclosure in detail, the present disclosure briefly summarized above can be described in more detail with reference to the embodiments, some of which are shown in the accompanying drawings. However, it should be noted that the accompanying drawings only show exemplary embodiments and are therefore not to be considered as limiting the scope thereof, and other equally effective embodiments may be allowed.

[0006] Figure 1 An example system for performing light-efficient fluorescence imaging in accordance with certain embodiments is presented.

[0007] FIG. 2A to FIG. 2C According to some embodiments Figure 1 A graph of the spectrum of the system's return light combined with the wavelength response of the optical filter.

[0008] Figure 2D Demonstrates the use of certain embodiments Figure 1 The equivalent passband obtained by the system.

[0009] Figure 3 An alternative system for performing light-efficient fluorescence imaging according to certain embodiments is presented.

[0010] Figure 4A and Figure 4B According to some embodiments Figure 3 A plot of the spectrum of the system's return light combined with the wavelength response of the notch filter.

[0011] Figure 5 Demonstrating some embodiments of the Figure 1 and Figure 3 The system is targeted at the equivalent passband of the sensitivity spectrum of the sensor in the color camera.

[0012] Figure 6 is a process flow diagram of a method for performing light-efficient fluorescence imaging according to certain embodiments.

[0013] Figure 7 An example computing device that at least partially implements one or more functions for implementing light-efficient fluorescence imaging in accordance with certain embodiments is presented.

[0014] To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements and features of one embodiment may be beneficially incorporated in other embodiments without further recitation. DETAILED DESCRIPTION

[0015] Fundus autofluorescence imaging (FAF) has become an important tool for diagnosing retinal degenerative diseases. FAF involves illuminating the retina with light and detecting the resulting autofluorescence. The excited autofluorescence can come from multiple sources (e.g., disease biomarkers). In order to detect disease at an early stage and make a better diagnosis, it is best to analyze the spectrum of fluorescence to establish the spectral "fingerprint" of different biomarkers to determine which disease marker is the main contributor to the fluorescence.

[0016] In existing methods, fluorescence imaging uses single wavelength (narrow band) light to excite the tissue of the retina and uses a wide band to detect the fluorescence emission. In existing methods, a spectrometer is used at the detector to measure the spectrum of the fluorescence signal. However, it is generally difficult to simultaneously resolve the spectrum and capture the spatial information of the fundus. The systems and methods disclosed herein enable the fluorescence of the eye to be imaged with high spatial accuracy using relatively simple equipment that does not include a spectrometer.

[0017] Multispectral imaging (MSI) is another existing method for imaging the retina in multiple wavelength bands. Typical MSI techniques illuminate the eye with narrowband light of multiple different wavelength bands. The light is detected by a detector after passing through a transmission filter that matches the narrowband light. However, for fluorescence imaging, this technology cannot be directly applied. Fluorescence imaging is performed by flashing high-intensity excitation light. Collecting only narrowband fluorescence signals that pass through a transmission filter such as that used for MSI is not light efficient. Capturing fluorescence in multiple wavelength bands in this way will require multiple flashes and may cause phototoxicity. The systems and methods disclosed herein enable imaging of fluorescence with high light efficiency and without causing phototoxicity.

[0018] Figure 1 An example system 100 for performing light-efficient fluorescence imaging of a retina 102 of a patient's eye 104 without the use of a spectrometer is shown. System 100 includes a light source 106. Light source 106 can be implemented as one or more light emitting diodes (LEDs) or other types of light sources. Light source 106 can be narrow band (e.g., -3dB bandwidth less than 100nm, 50nm, 25nm, or 10nm) or a single wavelength, or a combination of both. Light from the light source can be in the visible spectrum (e.g., between 380nm and 700nm), or can be in the infrared spectrum. Filter 106a can filter light from light source 106 to reduce light that does not contribute to exciting fluorescence emission.

[0019] Light from the light source 106 can be transmitted to the eye 104 via a beam splitter 110, which can be implemented as a dichroic mirror. The beam splitter 110 can operate as a filter for light returning from the eye 104, and can attenuate light in the passband of the filter 106a (e.g., attenuate by at least 10 dB) while not substantially attenuating light in one or more other wavelength bands corresponding to fluorescence of the retina 102 (e.g., attenuate by less than 3 dB). A portion of the light returning from the retina 102 passes through the beam splitter 110. As used herein, "return light" refers to light that has been filtered by the beam splitter 110 (transmitted in the illustrated example) and / or one or more other filtering steps, and will primarily constitute light emitted by the retina 102 as fluorescence, e.g., light other than fluorescence in the return light is attenuated by at least 6 dB more than the fluorescence.

[0020] The returned light is incident on the optical filter 112. A portion of the returned light is blocked by the optical filter 112 and is incident on the camera 114. A portion of the returned light is transmitted through the optical filter 112 and is incident on the camera 116. The cameras 114, 116 may be color (red, green, blue) cameras, monochrome cameras, infrared cameras, or other types of cameras. Other optical elements (such as lenses, pinhole filters, mirrors, etc.) may be present in the system 100 to focus the light on the retina 102, suppress reflections from structures other than the retina 102 (e.g., the cornea), and focus the light on the detectors of the cameras 114, 116.

[0021] The optical filter 112 may be implemented as a dichroic mirror or other types of optical filters. The optical filter 112 may be a low pass filter, a high pass filter, a notch filter, or other types of filters. Figure 1 As shown, the optical axis of the optical filter 112 can be at a non-parallel angle relative to the optical axis of the cameras 114, 116, such as between 42 degrees and 48 degrees, between 44 degrees and 46 degrees, or at an angle of 45 degrees. The system 100 can include multiple optical filters 112, which can be selectively placed in the illustrated positions or other positions to perform fluorescence imaging as described in more detail below.

[0022] FIG. 2A to FIG. 2D The operation of system 100 is shown. FIG. 2A to FIG. 2D The interpretation is made with reference to the spectrum R of light returned from a point on the retina 102 (e.g., the spectrum of fluorescence returned from a point on the retina 102). This spectrum will be approximated by the cameras 114, 116 as a single monochrome pixel or red, green, and blue intensities according to the sensitivity spectrum of the cameras 114, 116 (see Figure 5 and corresponding discussion).

[0023] See Figure 2A In the case where the optical filter 112 is a high-pass filter or a low-pass filter, one of the cameras 114 and 116 (the "first camera") will mainly capture light within the low-pass wavelength band LPA, while light with wavelengths higher than the low-pass wavelength band LPA is attenuated by the optical filter 112. The other camera 116 and 114 (the "second camera") will mainly capture light within the high-pass wavelength band HPA, while light with wavelengths lower than the high-pass wavelength band HPA is attenuated by the optical filter 112. The optical filter 112 may define a cut-off wavelength COA (e.g., a -3dB cut-off wavelength) that defines the boundary between the wavelength bands LPA and HPA.

[0024] See also Figure 2B and Figure 2C, other optical filters 112 may be used, each having a different cutoff wavelength COB, COC between the corresponding low passband LPB, LPC and the different high passband HPB, HPC. For example, the cutoff wavelength may be such that COA <COB<COC。

[0025] Although the wavelength responses of three different filters 112 are shown, more or fewer filters 112 may be used. The system 100 may be used to flash the retina 102 with the light source 106 for each filter 112 so that images are captured with the cameras 114, 116 for each filter 112. Accordingly, the intensity of the light source 106 and the number of filters 112 may be selected to avoid phototoxicity.

[0026] See also Figure 2D , images captured using cameras 114, 116 for each filter 112 can be combined to achieve an estimated image representing light within equivalent passbands PB1 to PB4, which are greater in number than the number of filters 112. It is further noted that when images are captured using filters 112, the wavelength range collected by each camera 114, 116 is wider than the equivalent passbands PB1 to PB4, which is more light efficient. That is, the amount of returned light collected relative to the amount of light illuminating the retina 102 is higher than in the case of passband filters having equivalent passbands PB1 to PB4. Accordingly, the degree of phototoxicity relative to the amount of spectral information obtained is lower than in the case of using passband filters.

[0027] The images obtained using the filter 112 and the cameras 114, 116 may be combined in various ways. In the following explanation, the following notation is used:

[0028] ILA represents an image obtained with the first camera for the low pass wavelength band LPA (eg, an image captured with camera 114 if filter 112 is a high pass filter, an image captured with camera 116 if filter 112 is a low pass filter).

[0029] IHA represents an image obtained with the first camera for the low-pass wavelength band HPA (eg, an image captured with camera 114 if filter 112 is a low-pass filter, or an image captured with camera 116 if filter 112 is a high-pass filter).

[0030] ILB represents an image obtained with the first camera for the low-pass wavelength band LPB.

[0031] IHB represents the image obtained with the first camera for the low-pass wavelength band HPB.

[0032] ILC represents an image obtained with the first camera for the low-pass wavelength band LPC.

[0033] IHC represents the image obtained with the first camera for the low-pass wavelength band HPC.

[0034] IP1, IP2, IP3, IP4 represent images of light estimated to be in equivalent passbands PB1, PB2, PB3, PB4, respectively.

[0035] In the first method, a first image of a low-pass wavelength band having a first cutoff wavelength (the second cutoff wavelength is higher than the first cutoff wavelength) is subtracted from an image of a low-pass wavelength band having a second cutoff wavelength to obtain a passband image corresponding to a wavelength band between the first cutoff wavelength and the second cutoff wavelength. For example, IP1, IP2, IP3, IP4 can be obtained as follows:

[0036] IP1 can be equivalent to ILA

[0037] IP2=ILB-ILA

[0038] IP3=ILC-ILB

[0039] IP4 can be equivalent to IHC

[0040] In the second method, a first image of a high-pass wavelength band having a first cutoff wavelength (the second cutoff wavelength is lower than the first cutoff wavelength) is subtracted from an image of a high-pass wavelength band having a second cutoff wavelength to obtain a passband image corresponding to a wavelength band between the first cutoff wavelength and the second cutoff wavelength. For example, IP1, IP2, IP3, IP4 can be obtained as follows:

[0041] IP1 can be equivalent to ILA

[0042] IP2=IHA-IHB

[0043] IP3=IHB-IHC

[0044] IP4 can be equivalent to IHC

[0045] The third method is a combination of the first method and the second method. The image corresponding to the wavelength passband according to the first method can be added together (or weighted and added) with the image for the same wavelength passband according to the second method, and the resulting image can be scaled, such as divided by two or some other scaling factor. For example, IP1, IP2, IP3, IP4 can be obtained as follows:

[0046] IP1 can be equivalent to ILA

[0047] IP2 = (IHA-IHB+ILB-ILA) / 2

[0048] IP3 = (IHB-IHC+ILC-ILB) / 2

[0049] IP4 can be equivalent to IHC

[0050] The third method has the advantage of using information from four different images, thereby achieving higher accuracy and allowing lower flicker light intensity. In addition to the benefit of reducing the number of flickers, the third method provides further advantages over the use of an equivalent passband filter. The frequency response of a passband filter is not completely flat, which means that even within the nominal passband, light at the edge wavelength of the passband will be attenuated more than light in the center of the passband. Using the third method, light at wavelengths that are significantly offset from the cut-off wavelengths COA, COB, COC and located at the limits of the equivalent passband is utilized, and such light attenuation is relatively less than that of an equivalent passband filter.

[0051] As used herein, image addition and subtraction may be understood as pixel-by-pixel addition and subtraction such that, for image A and image B, the pixel value D(x, y) in the difference (or sum) image D is equal to the difference (or sum) between the pixel value A(x, y) and the pixel value B(x, y) in image A, where x and y are indices of the values ​​in the two-dimensional pixel arrays constituting images A, B, and D.

[0052] Although the examples described herein involve addition and subtraction, other pixel-by-pixel operations may be performed in a similar manner, such as D(x,y)=A(x,y) / B(x,y), D(x,y)=A(x,y)*B(x,y), or D(x,y)=F(A(x,y),B(x,y)), where F() is a mathematical function selected to enhance the visibility of retinal features.

[0053] In some embodiments, the images may be weighted before being combined. Such weighting may compensate for the different sensitivities of the cameras 114, 116, or otherwise improve the ability of the combined image to approximate the results obtained using a spectrometer. For example, an image of the retina 102 may be obtained using the system 100 and processed to obtain combined images IP1, IP2, IP3, IP4. For the same retina 102, the spectrum of the returned light at a certain point on the retina 102 may be obtained, for example, using a spectrometer. The intensity of the returned light within each equivalent passband PB1, PB2, PB3, PB4 may be integrated and compared with the pixel intensity of the pixel representing the point or the pixel block representing the area containing the point in the images IP1, IP2, IP3, IP4.

[0054] The weights of the images can be selected so that after weighting, the relative intensity of the pixels or blocks of pixels in the images IP1, IP2, IP3, IP4 corresponds to the relative size of the reflectivity integral within each equivalent passband PB1, PB2, PB3, PB4. Multiple points within the image can be processed in a similar manner. Points from one or more other images can be processed in a similar manner to obtain weights. The final weight can be obtained as an average or other combination of weights obtained for multiple points in a single image or multiple images.

[0055] See also Figure 3 In some embodiments, similar accuracy can be achieved using system 300. System 300 reduces complexity by using a single camera 302. Although system 300 requires subjecting retina 102 to more flashes than system 100, it still provides an improvement over obtaining images using conventional MSI without a spectrometer.

[0056] The system 300 can illuminate the retina 102 using a light source 106 (and possibly a corresponding filter 106a as described above) and a beam splitter 110. The light returning from the retina 102 passes through the beam splitter 110 (which can be a dichroic mirror that filters the passband of the filter 106a as described above), which produces light that mainly contains fluorescence (i.e., "return light" as defined above). A single camera 302 detects the portion of the return light that is transmitted through the optical filter 112 or blocked by the optical filter. The system 300 can capture images for wavelength bands (LPA, LPB, LPC, HPA, HPB, HPB) by selecting the optical filter 112 and the orientation of the optical filter 112. For example, a low-pass optical filter 112 with a cutoff wavelength COA can be placed together with a camera 302 that receives the transmitted light to obtain an image ILA. A high-pass optical filter 112 with a cutoff wavelength COA can be placed together with a camera 302 that receives the transmitted light to obtain an image IHA. Alternatively, the camera 302 may be moved to receive the reflected light to obtain the image IHA using the same optical filter 112 as used to obtain ILA. The images ILB, IHB, ILC, IHC may be obtained in a similar manner using filters with cut-off wavelengths COB and COC. The images ILA, IHA, ILB, IHB, ILC, IHC obtained using the system 300 may be processed in the same manner as the images obtained using the system 100 to obtain images corresponding to the equivalent passbands PB1, PB2, PB3, PB4.

[0057] Figure 4A and Figure 4B It is shown how the optical filter 112 implemented as a notch filter can be used to obtain an image for a given passband. Figure 4A , a first image of the retina 102 can be obtained using the system 100 or 300 by capturing the return light in the unfiltered wavelength band UF. The first image can be obtained (a) without the optical filter 112 or (b) with the optical filter 112 having substantially no attenuation (e.g., less than 1 dB attenuation) for a wavelength range including the entire stop band of the notch filter.

[0058] See Figure 4B , a second image of the retina 102 can be obtained using system 100 or 300 by capturing a portion of the return light in wavelength bands NFL and NFH and substantially excluding (e.g., at least -3 dB attenuation and / or at least -6 dB average attenuation) light in a stop band RB between pass band NFL and pass band NFH.

[0059] An image representing the return light within the stop band can be obtained by subtracting the second image from the first image. Figure 2D The first image and the second image are weighted using the weights determined by the description.

[0060] See also Figure 5 , where the cameras 114, 116 or the camera 302 are color cameras, the red sensor, the green sensor and the blue sensor have different sensitivity spectra. For example, any of the cameras 114, 116, 302 may be implemented as the NGENUITY 3D visualization system provided by Alcon Inc. of Fort Worth, Texas, USA. The pixel values ​​of an image of a given color may be considered as separate images that may be processed as described above. The equivalent passbands PB1, PB2, PB3, PB4 may be selected with reference to the sensitivity spectra so that one or more of the sensitivity spectra (e.g., -3dB bandwidth) of each sensor are divided into two or more passbands. For the red image, the green image and the blue image constituting the color image obtained using the system 100 or 300, images for the equivalent passbands may be obtained as described above. In this way, assuming four equivalent passbands, up to twelve images may be obtained for a single color image, each image representing light from a different portion of the electromagnetic spectrum. In practice, images of a given color will not contain significant information for passbands away from the peak sensitivity for that color, so fewer images will be acquired and used.

[0061] For example, in Figure 5In the example of , the blue image can be used to obtain images corresponding to passbands PB1 and PB2, the green image can be divided into images corresponding to PB2 and PB3, and the red image can be divided into images corresponding to PB3 and PB4. It should be noted that although, for example, the blue image and the green image are both used to generate an image corresponding to PB2, these images may have different information about fluorescence because the sensitivity spectra of the blue sensor and the green sensor are different.

[0062] For a given equivalent passband PB1, PB2, PB3, PB4, the combined sensitivity spectrum of the sensor in the frequency domain is the product of the frequency response of the equivalent passband and the sensitivity of the sensor in the frequency domain. The frequency response of the equivalent passband can be determined based on the frequency response of the optical filter 112 used to achieve the equivalent passband.

[0063] The combined sensitivity for each color and each passband can be used to obtain more detailed spectral information for the red image, the green image, and the blue image. In particular, for each color and equivalent passband, combining the sensitivity of the sensor for that color and the frequency response of the equivalent passband (along with the spectrum of the light source 106) can be used to find a spectral basis function. The spectral basis functions for the combination of color and equivalent passband can then be used to obtain multispectral information from images obtained for some or all combinations of color and equivalent passband.

[0064] refer to Figure 6 , method 600 may be performed by a computing system (e.g., computing system 700) that receives images from cameras 114, 116 of system 100 or camera 302 of system 300. Some embodiments described above use different filter configurations, such as some or all of the following: different optical filters 112, different orientations of optical filter 112 relative to camera 302 (operating as a high pass filter or a low pass filter), and / or omitting optical filter 112 in some configurations. In such embodiments, electronic actuators may be used to automatically move or rotate optical filter 112 and / or move or rotate camera 302 to achieve different filter configurations. Computing system 700 may be coupled to the electronic actuators to achieve different filter configurations when performing method 600. Computing system 700 may be further coupled to light source 106 and configured to illuminate retina 102 with light source 106 when capturing images as described above.

[0065] Method 600 may include configuring optical filter 112 of one or more available optical filters 112 at step 602, and capturing one or more images of retina 102 using camera 114, 116, or camera 302 according to the filter configuration of step 602 at step 604. Step 604 includes emitting flashes from light source 106 to excite fluorescence of retina 102. Steps 602 and 604 may be repeated, with each iteration of step 602 implementing a different filter configuration, such as described above with respect to FIG. 2A to FIG. 2C as well as Figure 4A and Figure 4B Some or all of the described filter configurations.

[0066] Method 600 may include, at step 606, weighting the images obtained in one or more iterations of step 604. In some embodiments, step 606 is omitted. Where step 606 is performed, the weights may be determined as described above.

[0067] The images, which may have been weighted in step 606, may then be combined in step 608 to obtain combined images, each of which corresponds to light having a wavelength within an equivalent passband. For example, step 606 may include combining the images using the method described above to obtain some or all of IP1, IP2, IP3, IP4, or more equivalent passband images.

[0068] The combined image from step 608 may then be displayed at step 610, such as on a display device of computing system 700. Other processing may be performed, such as: using a machine learning model for feature recognition; using a machine learning model to process the combined image and / or the identified features to identify a disease represented in the combined image; or other processing. The display of the combined image may be subject to control of an interface through which a user may select an equivalent passband to invoke display of an image corresponding to the equivalent passband.

[0069] Figure 7 An example computing system 700 is shown that at least partially implements one or more functions described herein. The computing system 700 may be integrated with an imaging device that captures images according to one or more of the imaging modalities described herein, or may be a separate computing device.

[0070] As shown, the computing system 700 includes a central processing unit (CPU) 702, one or more I / O device interfaces 704 that can allow various I / O devices 714 (e.g., keyboard, display, mouse device, pen input, etc.) to be connected to the computing system 700, a network interface 706 through which the computing system 700 is connected to a network 790, a memory 708, a storage device 710, and an interconnect 712.

[0071] CPU 702 can retrieve and execute programming instructions stored in memory 708. Similarly, CPU 702 can retrieve and store application data residing in memory 708. Interconnect 712 transmits programming instructions and application data between CPU 702, I / O device interface 704, network interface 706, memory 708, and storage device 710. CPU 702 is included to represent a single CPU, multiple CPUs, a single CPU with multiple processing cores, etc.

[0072] The memory 708 represents a volatile memory such as a random access memory and / or a non-volatile memory such as a non-volatile random access memory, a phase change random access memory, etc. As shown, the memory 708 may store executable code image capture logic 716, such as logic for performing steps 602 and 604 of the method 600. The memory 708 may store executable code implementing a combination logic 718 for combining images to obtain a passband image, such as described above with respect to Figure 2D , Figure 4A and Figure 4B , Figure 5 as well as Figure 6 as described in step 608.

[0073] Storage device 710 may be a non-volatile memory such as a disk drive, a solid state drive, or a collection of storage devices distributed across multiple storage systems. Storage device 710 may store images 720 and combined images 722 obtained using system 100 or 300, as described above with respect to Figure 2D , Figure 4A and Figure 4B , Figure 5 as well as Figure 6 as described in step 608.

[0074] Additional considerations

[0075] The foregoing description is provided to enable any person skilled in the art to practice the various embodiments described herein. Various modifications to these embodiments are clear to those skilled in the art, and the general principles defined herein may be applied to other embodiments. For example, without departing from the scope of the present disclosure, the functions and arrangements of the elements discussed may be changed. Various examples may appropriately omit, replace or add various programs or components. In addition, the features described with respect to some examples may be combined in some other examples. For example, any number of aspects set forth herein may be used to implement a device or practice method. In addition, the scope of the present disclosure is intended to cover such devices or methods practiced using other structures, functions, or structures and functions in addition to or different from the various aspects of the present disclosure set forth herein. It should be understood that any aspect of the present disclosure disclosed herein may be embodied by one or more elements of a claim.

[0076] As used herein, a phrase referring to "at least one of" a list of items refers to any combination of those items, including single members. For example, "at least one of a, b, or c" is intended to cover any combination of a, b, c, ab, ac, bc, and abc, as well as multiples of the same element (e.g., aa, aaa, aab, aac, abb, acc, bb, bbb, bbc, cc, and ccc or any other order of a, b, and c).

[0077] As used herein, the term "determining" encompasses a wide variety of actions. For example, "determining" may include calculating, computing, processing, deriving, investigating, searching (e.g., searching in a table, database, or other data structure), ascertaining, etc. In addition, "determining" may include receiving (e.g., receiving information), accessing (e.g., accessing data in a memory), etc. In addition, "determining" may include parsing, selecting, choosing, establishing, etc.

[0078] The method disclosed herein includes one or more steps or actions for implementing the method. Without departing from the scope of the claims, the method steps and / or actions can be interchangeable with each other. In other words, unless a specific step or action sequence is specified, the order and / or use of specific steps and / or actions can be modified without departing from the scope of the claims. Further, the various operations of the above-mentioned method can be performed by any suitable device that can perform the corresponding function. These devices may include various hardware and / or software components and / or modules, including but not limited to circuits, application specific integrated circuits (ASICs) or processors. Generally, in the case of operations shown in the figure, those operations can have corresponding corresponding devices with similar numbers plus functional components.

[0079] The various illustrative logical blocks, modules, and circuits described in conjunction with the present disclosure may be implemented or executed with a general purpose processor, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA) or other programmable logic device (PLD), discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. The general purpose processor may be a microprocessor, but in an alternative, the processor may be any commercially available processor, controller, microcontroller, or state machine. The processor may also be implemented as a combination of computing devices, for example, a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[0080] The processing system can be implemented with a bus architecture. Depending on the specific application and overall design constraints of the processing system, the bus may include any number of interconnecting buses and bridges. The bus may link together various circuits including a processor, a machine-readable medium, and an input / output device. A user interface (e.g., a keyboard, a display, a mouse, a joystick, etc.) may also be connected to the bus. The bus may also link various other circuits such as timing sources, peripherals, voltage regulators, power management circuits, etc., which are well known in the art and therefore will not be further described. The processor may be implemented with one or more general and / or special processors. Examples include microprocessors, microcontrollers, DSP processors, and other circuit systems that can execute software. Those skilled in the art will recognize how to best implement the described functions of the processing system according to the specific application and the overall design constraints imposed on the entire system.

[0081] If implemented in software, the function may be stored as one or more instructions or codes on a computer-readable medium or transmitted via a computer-readable medium. Software should be broadly interpreted as instructions, data, or any combination thereof, whether referred to as software, firmware, middleware, microcode, hardware description language, or other. Computer-readable media include both computer storage media and communication media (such as any medium that facilitates the transfer of computer programs from one place to another). The processor may be responsible for managing the bus and general processing, including the execution of software modules stored on a computer-readable storage medium. A computer-readable storage medium may be connected to a processor so that the processor can read information from the storage medium and write information to the storage medium. In an alternative, the storage medium may be integrated into the processor. For example, a computer-readable medium may include a transmission line, a carrier modulated by data, and / or a computer-readable storage medium on which instructions separated from a wireless node are stored, all of which may be accessed by a processor via a bus interface. Alternatively or in addition, a computer-readable medium or any portion thereof may be integrated into a processor, such as a case where a cache and / or a general register file may be provided. For example, examples of machine-readable storage media may include RAM (random access memory), flash memory, ROM (read-only memory), PROM (programmable read-only memory), EPROM (erasable programmable read-only memory), EEPROM (electrically erasable programmable read-only memory), registers, magnetic disks, optical disks, hard drives, or any other suitable storage media, or any combination thereof. Machine-readable media may be embodied in a computer program product.

[0082] A software module may include a single instruction or multiple instructions, and may be distributed over several different code segments, between different programs, and across multiple storage media. A computer-readable medium may include multiple software modules. A software module includes instructions that, when executed by a device such as a processor, cause a processing system to perform various functions. A software module may include a transmission module and a reception module. Each software module may reside in a single storage device, or may be distributed in multiple storage devices. For example, when a triggering event occurs, a software module may be loaded from a hard drive into a RAM. During the execution of a software module, a processor may load some instructions into a cache to increase access speed. Then, one or more cache lines may be loaded into a general register file for execution by the processor. When referring to the function of a software module, it should be understood that such function is implemented by the processor when executing instructions from the software module.

[0083] The following claims are not intended to be limited to the embodiments shown herein, but are given the full scope consistent with the language of the claims. In the claims, unless otherwise specified, reference to a singular element is not intended to mean "one and only one", but "one or more". Unless otherwise specifically stated, the term "some" refers to one or more. According to 35 U.S.C. § 112 (f), the elements of any claim will not be interpreted unless the phrase "device for..." is used to expressly describe these elements, or in the case of a method claim, the phrase "step for..." is used to describe these elements. All structural and functional equivalents of the elements of the various aspects described throughout the present disclosure that are known or will be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be covered by the claims. In addition, whether or not such disclosure is explicitly described in the claims, the content disclosed herein is not intended to be donated to the public.

Claims

1. A system comprising: One or more processing devices and one or more memory devices coupled to the one or more processing devices, the one or more memory devices storing executable code that, when executed by the one or more processing devices, causes the one or more processing devices to: receiving a first image of first light returned from a retina of a patient and filtered according to a first filtering; receiving a second image of second light returned from the patient's retina and filtered according to a second filtering; combining the first image and the second image to obtain a combined image representing a portion of at least one of the first light and the second light within a passband, neither the first filtering nor the second filtering comprising passband filtering; and A representation of the combined image is output to a display device.

2. The system of claim 1, wherein: The executable code, when executed by the one or more processing devices, further causes the one or more processing devices to combine the first image and the second image by subtracting the first image from the second image.

3. The system of claim 2, wherein: The first filtering is a high-pass filtering having a first cut-off wavelength, and the second filtering is a high-pass filtering having a second cut-off wavelength lower than the first cut-off wavelength, and the passband is between the first cut-off wavelength and the second cut-off wavelength.

4. The system of claim 2, wherein: The first filtering is a low-pass filtering having a first cut-off wavelength, and the second filtering is a low-pass filtering having a second cut-off wavelength higher than the first cut-off wavelength, and the passband is between the first cut-off wavelength and the second cut-off wavelength.

5. The system of claim 1, further comprising: a light source configured to illuminate the retina and coupled to the one or more processing devices; a camera coupled to the one or more processing devices; a first optical filter positionable between the camera and the retina; as well as a second optical filter positionable between the camera and the retina; Wherein the executable code, when executed by the one or more processing devices, further causes the one or more processing devices to receive the first image when the first optical filter is positioned between the retina and the camera and to receive the second image when the second optical filter is positioned between the retina and the camera.

6. The system of claim 1, further comprising: a light source configured to illuminate the retina and coupled to the one or more processing devices; a first camera coupled to the one or more processing devices; a second camera coupled to the one or more processing devices; a first optical filter positionable with the first camera receiving light transmission from the first optical filter and the second camera receiving light reflection from the first optical filter; as well as a second optical filter positionable with the first camera receiving light transmission from the second optical filter and the second camera receiving light reflection from the second optical filter; Wherein, when the executable code is executed by the one or more processing devices, the one or more processing devices further cause the one or more processing devices to: receiving the first image from the first camera and a third image from the second camera with the first optical filter positioned between the first camera and the retina; receiving the second image from the first camera and a fourth image from the second camera with the second optical filter positioned between the first camera and the retina; and The first image, the second image, the third image, and the fourth image are combined to obtain the combined image.

7. The system of claim 6, wherein: The first optical filter and the second optical filter are low-pass filters, and the cut-off wavelength of the first optical filter is higher than the cut-off wavelength of the second optical filter; The executable code, when executed by the one or more processing devices, further causes the one or more processing devices to combine the first image, the second image, the third image, and the fourth image by adding the first image and the fourth image and subtracting the second image and the third image to obtain the combined image.

8. The system of claim 6, wherein: The first optical filter and the second optical filter are high-pass filters, the cutoff wavelength of the first optical filter is higher than the cutoff wavelength of the second optical filter; and The executable code, when executed by the one or more processing devices, further causes the one or more processing devices to combine the first image, the second image, the third image, and the fourth image by adding the third image and the second image and subtracting the first image and the fourth image to obtain the combined image.

9. The system of claim 6, wherein: The first optical filter and the second optical filter are dichroic mirrors.

Images